Podocalyxin (PODXL) Nonsense Variant in Patients With Atypical Adult-Onset Focal Segmental Glomerulosclerosis (FSGS)
Bibliographic record
Abstract
Introduction: Genetic kidney disease has been the focus of many investigative efforts, particularly in patients with adult-onset chronic kidney disease (CKD) and positive family history. FSGS is a podocyte-driven disease, that is the most frequent cause of CKD worldwide and regularly progresses to end-stage kidney disease (ESKD). The PODXL-encoded podocalyxin is a podocyte protein and a member of the CD34 family of stem cell sialomucins. It has recently been described in families with both recessive (compound heterozygous variants) and dominant forms of familial nephropathies. We detected a novel heterozygous nonsense variant in the PODXL gene c.1048C>T, p.(Arg350*).in a family with atypical FSGS. Case Description: We detected a novel heterozygous nonsense variant in the PODXL gene c.1048C>T, p.(Arg350*) in a family with atypical FSGS. This variant was segregated in this family with 3 affected individuals with CKD all carrying the same variant. The patient is a 43-year-old woman, who was first diagnosed 29 years with proteinuria, peripheral edema, and normal creatinine level. A kidney biopsy raised the suspicion of FSGS with patchy podocyte effacement but no definite segmental sclerotic glomerular lesions were identified., There were some areas of thickening of the glomerular basement membranes and mild tubular atrophy and interstitial fibrosis. Initially, she commenced prednisone but had no response, treatment switched to mycophenolate but no response, then started on cyclosporine with low dose prednisone with a complete response followed by relapse. She was later switched to tacrolimus with partial response. Discussion: Next-generation sequencing (NGS) technology can reveal the underlying etiology of disease in patients, where other diagnostic strategies have failed to confirm the diagnosis. In this case, histopathology following kidney biopsy raised the suspicion of FSGS but diagnosis could not be confirmed. Increased utilization of NGS is expected to increase diagnostic efficiency in patients with CKD, especially in patients with positive family history and/or young-onset ESKD. A definitive genetic diagnosis has important prognostic value to help understand these atypical subtypes of disease which may in turn impact treatment strategies for patients carrying particular genetic variants.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".